Accelerating Colorectal Cancer Screening through Implementation Science in Appalachia This multi-site project aims to increase screening and follow-up for colorectal cancer (CRC) in central Appalachia, a medically underserved region recognized as one of three distinct ?hotspots? for CRC mortality. Specifically, the Appalachian Regional Commission classifies 32 eastern Ohio (OH) counties and the 54 counties in eastern Kentucky (KY) as north central and central Appalachia, respectively. CRC incidence and mortality rates in the area are among the highest in the nation, and neither state meets the national target of 80% of eligible residents screened for CRC. There have been few randomized intervention trials addressing multiple levels of influence on CRC screening behaviors and outcomes in this region. To address this gap, investigators at the University of Kentucky and The Ohio State University will build on a 12-year collaborative history, strong relationships with Appalachian communities and health clinics, and extensive experience with community-based cancer prevention and control intervention research to develop, implement, and evaluate a multilevel intervention (MLI) ? adapted from evidence-based interventions that include components targeting clinics and providers (in-reach) and the community (outreach) ? to increase CRC screening, follow-up and referral-to-care among patients age 50-74 in 12 counties in Appalachian KY and OH. The overall goals of this project are to contribute to the evidence-base for a MLI that increases rates of CRC screening, follow-up, and referral-to-care, particularly in rural, medically underserved populations, and help showcase best practices for how MLIs can be scaled-up to reduce the burden of CRC in the U.S. For the Planning-Exploratory Phase (UG3) in Year 1, our specific aims are to: 1) Pilot test, measure, and refine a MLI to increase rates of CRC screening, follow-up and referral-to-care in Appalachian OH and Appalachian KY; and 2) Provide evidence supporting transition to the Implementation Phase (UH3) [per NCI approval]. For the Implementation Phase (UH4) in Years 2-5, our specific aims are to: 1) Test the revised MLI in a group randomized trial, delayed intervention to assess the impact of the MLI on increasing rates of CRC screening, follow-up, and referral-to-care among Appalachian KY and Appalachian OH populations; and 2) Assess dissemination and sustainability of the intervention. The project will be implemented in collaboration with community and clinical partners in 12 counties, 6 in Ohio and 6 in Kentucky. Counties will be randomized to early or delayed intervention after baseline data collection. The main outcome will be CRC screening as defined by US Preventive Services Task Force guidelines and measured by clinic electronic health records and county- level behavioral assessments using random digit dialed telephone surveys similar to CDC?s Behavioral Risk Factor Surveillance System. Our work will be accomplished through collaboration with the ACCSIS Coordinating Center, other ACCSIS Research Projects, ACCSIS Steering Committee and Workgroups, NCI, and community partners. If effective, this MLI will be disseminated to our clinical and community partners throughout Appalachia.